Squamous cell carcinoma (SCC) is a form of cancer that occurs in many different organs, including the skin, lips, mouth, esophagus, head and neck, urinary bladder, prostate, lungs, breast, vagina, cervix, and ovaries. It is a malignant tumor of the squamous epithelium. Squamous cell carcinomas may be located in situ (confined to the original site) or invasive. Squamous cell carcinomas in situ are also called Bowen's disease. In contrast to other epithelial carcinomas such as basal cell carcinomas, squamous cell carcinomas have a greater risk for metastasis and thus early diagnosis is important in the effective treatment of SCC.
Breast cancer and cervical cancer are the most common forms of cancer in women. Primary breast or cervical squamous cell carcinomas are rare; however, when they do occur they are associated with high mortality rates due to the aggressive nature of these cancers (Aparicio et al., Eur J Obstet Gynecol Reprod Biol., 137(2):222-6, 2008). Primary ovarian squamous cell carcinoma also occurs infrequently, and is difficult to detect preoperatively. Given the issues related to ovarian SCC diagnosis, most patients are not affirmatively diagnosed until the disease is advanced, which in turn increases the mortality rate of this form of cancer in women to about 58% in the United States.
In men, primary prostate cancer accounts for less than 1% of all prostate cancer cases and is associated with poor prognosis. The introduction of a serum-based test to detect Prostate Specific Antigen (PSA) led to a marked increase in the number of ambiguous test samples. Accordingly, additionally pathological study of these samples is necessary to positively identify a primary prostate squamous cell carcinoma sample.
Many of the primary SCCs rely on a combination of pathological findings, adjuvant treatments such as radiation, surgery or chemotherapy, and/or the presence or absence of multiple serum markers to aid in the diagnosis of a primary SSCs (Suzuki et al., Gynecol. Oncol., 77(3):405-9, 2000; Tas et al., J. Exp. Clin. Cancer Res., 19(4):477-81, 2000; Megha et al., Pathologica., 96(2):45-8, 2004).
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world and is a major cause of significant morbidity. In the United States, HNSCC accounts for over 90% of all head and neck cancers. It is estimated that 35,310 new cases will be diagnosed and that 7,500 deaths will result from HNSCC in the United States in 2008 (Jemal et al., (2008) CA Cancer J Clin, 58:71-96; Marur (2008) Mayo Clinic proceedings 83:489-501). Patients with HNSCC have a 60% mortality rate even with standard therapy such as radiation, surgery and/or chemotherapy. HNSCC has been linked to tobacco and betel nut use, alcohol consumption, frequent mouthwash use, and exposure to human papillomavirus (HPV), and individuals having a long-standing history of smoking and alcohol use are at the greatest risk for developing HNSCC (Marur (2008) Mayo Clinic proceedings 83:489-501; Spitz (1994) Seminars in Oncology 21:281-288).
New approaches in the treatment of advanced HNSCC include chemotherapy and surgical treatments that are designed to achieve organ preservation and to improve overall survival (Forastiere, et al., (2001) The New England Journal of Medicine, 345:1890-1900). Disappointingly, although these treatments enhance quality of life and moderate pain, survival rates have not improved for this type of cancer (Jemal, et al., (2005) CA Cancer J Clin 55:10-30; Patel (2001) Crit. Rev Oral Biol Med 12:55-63). There has been no significant improvement in 5-year survival over the past 20 years, despite aggressive and multidisciplinary treatment approaches (Friedlander (2003) Arch Otolaryngol Head Neck Surg, 129:363-366; Rodrigo, et al., (2003) Acta Otolaryngol 123:100-105; Schliephake (2003) Int J Oral Maxillofac Surg 32:233-245). There is currently no effective molecular marker for HNSCC.
Given the foregoing, it would be desirable to have a marker to permit screening and early diagnosis of primary SCCs such as HSNCC, as well as for staging and prognosing the disease.